Abstract

Introduction

Erythropoietin (Epo) has neurotrophic effects and may be a novel therapeutic agent in the treatment of depression. We have found antidepressant-like effects of Epo on emotional processing and mood in healthy volunteers.

Objective

The current study aimed to explore the effects of Epo on the neural processing of emotional information in depressed patients.

Materials and methods

Seventeen patients with acute major depressive disorder were randomised to receive Epo (40,000 IU) or saline iv in a double-blind, parallel-group design. On day 3, we assessed neural responses to positive, negative and neutral pictures during fMRI followed by picture recall after the scan. Mood and blood parameters were assessed at baseline and on day 3.

Results

Epo reduced neural response to negative vs. positive pictures 3 days post-administration in a network of areas including the hippocampus, ventromedial prefrontal and parietal cortex. After the scan, Epo-treated patients showed improved memory compared with those that were given placebo. The effects occurred in the absence of changes in mood or haematological parameters, suggesting that they originated from direct neurobiological actions of Epo.

Conclusions

These findings are similar to the effects of conventional antidepressants and opposite to the negative biases in depression. The central effects of Epo therefore deserve further investigation as a potential antidepressant mechanism.

Keywords

Antidepressant Human Emotion Depression Neuroimaging

Notes

Acknowledgements

We thank Drs. Digby Quested, Susan Shaw, Mary-Jane Attenburrow and Peter Sargent for their help with patient recruitment and Drs. Mike Browning, Danilo Arnone, Sarah McTavish and Matthew Taylor for the medical assistance. The study was supported by the Lundbeck Foundation, Denmark (grant no. 94/04).